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Investigation of biomarker for intra-articular fibrosis after anterior cruciate reconstruction

Research Project

Project/Area Number 19K18454
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Nakagawa Yusuke  東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (60822666)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords線維化 / 前十字靭帯損傷 / 炎症性サイトカイン / 関節液 / 前十字靱帯再建術 / 膝蓋下脂肪体線維化 / バイオマーカー / 前十字靭帯再建術 / 前十字靭帯再建再建術 / 関節内線維化 / 免疫細胞
Outline of Research at the Start

目的は前十字靭帯(ACL)再建術後の膝蓋下脂肪体(IFP)線維化に関わるバイオマーカーを探索し、ACL再建術の成績不良例の患者を早期に検出し、早期に介入を行うことで治療成績の向上を目指す。先行研究から我々はIFP線維化のマーカーとして術後の関節液中の炎症性サイトカインと免疫細胞に注目した。本研究にて以下の事象を明らかにする。
「関節液中の炎症性サイトカイン、免疫細胞と術後3ヵ月のIFP 線維化の程度との関連」
そのためにACL再建術患者の術後3日目、21日目に関節液を採取し、炎症性サイトカイン濃度、免疫細胞分画を測定。術後3ヶ月でMRIによるIFP線維化の評価と、臨床成績、疼痛を評価する。

Outline of Final Research Achievements

omplications after anterior cruciate ligament reconstruction (ACLR) includes intra-articular fibrosis leading to residual pain and delayed functional recovery. This study aimed to evaluate clinical outcomes and inflammatory cytokine levels in the synovial fluid of ACLR patients with or without severe IFP fibrosis. Patients were divided into two groups based on IFP fibrosis scoring. Synovial fluid was aspirated on the third or fourth postoperative day to measure inflammatory cytokines levels. Of the 36 patients included, 7 were allocated to the severe fibrosis group and 29 to the mild fibrosis group. Pain in the severe fibrosis group was greater and lower extension muscle strength than that in the mild fibrosis group. The severe fibrosis group demonstrated higher interleukin-1β, interleukin-6, and interferon-γ levels. Severe IFP fibrosis was associated with higher inflammatory cytokines in the synovial fluid and led to unfavorable clinical outcomes.

Academic Significance and Societal Importance of the Research Achievements

関節液中の炎症性サイトカインが高い患者でIFP線維化のリスクが高いことから、そのような患者に対して、MRIによるIFP線維化の評価。IFP線維化があればリハビリ、抗炎症薬の内服、ヒアルロン酸注射など早期に介入を行い、治療成績の改善につなげる。
炎症性サイトカインがIFP線維化の発生に関わる機序の一端が明らかとなった。今後さらに詳細なメカニズムを明らかにすることでIFP線維化を抑制する治療法の開発につながると考える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (22 results)

All 2021 2020 2019

All Journal Article (19 results) (of which Peer Reviewed: 18 results,  Open Access: 8 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Inhibition of fibrotic changes in infrapatellar fat pad alleviates persistent pain and articular cartilage degeneration in monoiodoacetic acid-induced rat arthritis model2021

    • Author(s)
      An J.-S.、Tsuji K.、Onuma H.、Araya N.、Isono M.、Hoshino T.、Inomata K.、Hino J.、Miyazato M.、Hosoda H.、Kangawa K.、Nakagawa Y.、Katagiri H.、Miyatake K.、Sekiya I.、Muneta T.、Koga H.
    • Journal Title

      Osteoarthritis and Cartilage

      Volume: 29 Issue: 3 Pages: 380-388

    • DOI

      10.1016/j.joca.2020.12.014

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extracellular vesicles derived from mesenchymal stromal cells mediate endogenous cell growth and migration via the CXCL5 and CXCL6/CXCR2 axes and repair menisci2021

    • Author(s)
      Kawata Kazumasa、Koga Hideyuki、Tsuji Kunikazu、Miyatake Kazumasa、Nakagawa Yusuke、Yokota Takanori、Sekiya Ichiro、Katagiri Hiroki
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 12 Issue: 1 Pages: 414-424

    • DOI

      10.1186/s13287-021-02481-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ultrasound-guided harvesting of synovium for regenerative medicine of cartilage and meniscus using synovial mesenchymal stem cells2021

    • Author(s)
      Ozeki N, Nakagawa Y, Mizuno M, Kohno Y, Katano H, Koga H, Sekiya I.
    • Journal Title

      Arthrosc Tech

      Volume: 10 Issue: 7 Pages: e1723-e1727

    • DOI

      10.1016/j.eats.2021.03.020

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical outcomes of two-stage revision total knee arthroplasty in infected cases with antibiotic-loaded cement spacers produced using a handmade silicone mold2021

    • Author(s)
      Hoshino Takashi、Watanabe Toshifumi、Nakagawa Yusuke、Katagiri Hiroki、Ozeki Nobutake、Ohara Toshiyuki、Shioda Mikio、Kono Yuji、Sekiya Ichiro、Koga Hideyuki
    • Journal Title

      Knee Surgery & Related Research

      Volume: 33 Issue: 1 Pages: 1-10

    • DOI

      10.1186/s43019-021-00113-3

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of Clinical Outcomes after Revision Anterior Cruciate Ligament Reconstruction using a Bone-patellar Tendon-bone Autograft and that Using a Double-Bundle Hamstring Tendon Autograft2021

    • Author(s)
      Katagiri Hiroki、Nakagawa Yusuke、Miyatake Kazumasa、Ozeki Nobutake、Kohno Yuji、Amemiya Masaki、Sekiya Ichiro、Koga Hideyuki
    • Journal Title

      The Journal of Knee Surgery

      Volume: none Issue: 06 Pages: 613-621

    • DOI

      10.1055/s-0041-1740927

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Arthroscopic Centralization Using Knotless Anchors for Extruded Medial Meniscus.2021

    • Author(s)
      Hideyuki Koga, Tomomasa Nakamura, Yusuke Nakagawa, Nobutake Ozeki, Toshiyuki Ohara, Mikio Shioda, Yuji Kohno, Masaki Amemiya, Ichiro Sekiya.
    • Journal Title

      Arthrosc Tech.

      Volume: 10 Issue: 3 Pages: e639-e645

    • DOI

      10.1016/j.eats.2020.10.051

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of different surgical procedures for meniscus injury on two-year clinical and radiological outcomes after anterior cruciate ligament reconstructions. -TMDU MAKS study2021

    • Author(s)
      Hoshino Takashi、Nakagawa Yusuke、Inomata Kei、Ohara Toshiyuki、Katagiri Hiroki、Otabe Koji、Ueki Hiroko、Hayashi Masaya、Nagase Tsuyoshi、Sekiya Ichiro、Ogiuchi Takashi、Muneta Takeshi、Koga Hideyuki、Hoshino Akiho、Yoshimura Hideya、Mochizuki Tomoyuki
    • Journal Title

      Journal of Orthopaedic Science

      Volume: 20 Issue: 1 Pages: 30376-30382

    • DOI

      10.1016/j.jos.2020.12.010

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Two-Year Outcomes After Meniscoplasty by Capsular Advancement With the Application of Arthroscopic Centralization Technique for Lateral Compartment Knee Osteoarthritis2020

    • Author(s)
      Koga Hideyuki、Nakamura Tomomasa、Katagiri Hiroki、Nakagawa Yusuke、Ozeki Nobutake、Ohara Toshiyuki、Shioda Mikio、Kohno Yuji、Amemiya Masaki、Sekiya Ichiro
    • Journal Title

      The American Journal of Sports Medicine

      Volume: 48 Issue: 13 Pages: 3154-3162

    • DOI

      10.1177/0363546520957367

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Trends in arthroplasty in Japan by a complete survey, 2014-20172020

    • Author(s)
      Hisako Katano, Nobutake Ozeki, Yuji Kohno, Yusuke Nakagawa, Hideyuki Koga, Toshifumi Watanabe, Tetsuya Jinno, Ichiro Sekiya
    • Journal Title

      J Orthop Sci .

      Volume: 20 Issue: 5 Pages: 812-822

    • DOI

      10.1016/j.jos.2020.07.022

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Knee laxity, lateral meniscus tear and distal femur morphology influence pivot shift test grade in ACL injury patients2020

    • Author(s)
      Cui Weiding、Nakagawa Yusuke、Katagiri Hiroki、Otabe Koji、Ohara Toshiyuki、Shioda Mikio、Kohno Yuji、Hoshino Takashi、Yoshihara Aritoshi、Sekiya Ichiro、Koga Hideyuki
    • Journal Title

      Knee Surgery, Sports Traumatology, Arthroscopy

      Volume: 29 Issue: 2 Pages: 633-640

    • DOI

      10.1007/s00167-020-05994-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intra-articular Injection of Pure Platelet-Rich Plasma Is the Most Effective Treatment for Joint Pain by Modulating Synovial Inflammation and Calcitonin Gene-Related Peptide Expression in a Rat Arthritis Model2020

    • Author(s)
      Araya Naoko、Miyatake Kazumasa、Tsuji Kunikazu、Katagiri Hiroki、Nakagawa Yusuke、Hoshino Takashi、Onuma Hiroaki、An Saisei、Nishio Hirofumi、Saita Yoshitomo、Sekiya Ichiro、Koga Hideyuki
    • Journal Title

      The American Journal of Sports Medicine

      Volume: 48 Issue: 8 Pages: 2004-2012

    • DOI

      10.1177/0363546520924011

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Investigation of association between the preoperative intra-articular anesthetic test and persistent pain after total knee arthroplasty2020

    • Author(s)
      Seki Yoshie、Katagiri Hiroki、Otabe Koji、Nakagawa Yusuke、Miyatake Kazumasa、Sekiya Ichiro、Koga Hideyuki
    • Journal Title

      Journal of Orthopaedic Science

      Volume: Epub Issue: 6 Pages: 1055-1060

    • DOI

      10.1016/j.jos.2020.01.013

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fibrotic changes in the infrapatellar fat pad induce new vessel formation and sensory nerve fiber endings that associate prolonged pain.2020

    • Author(s)
      Onuma H, Tsuji K, Hoshino T, Inomata K, Udo M, Nakagawa Y, Katagiri H, Miyatake K, Watanabe T, Sekiya I, Muneta T, Koga H
    • Journal Title

      J Orthop Res.

      Volume: In press Issue: 6 Pages: 1296-1306

    • DOI

      10.1002/jor.24580

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Synovial fluid-derived mesenchymal cells have non-inferior chondrogenic potential and can be utilized for regenerative therapy as substitute for synovium-derived cells.2020

    • Author(s)
      Amemiya M, Tsuji K, Katagiri H, Miyatake K, Nakagawa Y, Sekiya I, Muneta T, Koga H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 523 Issue: 2 Pages: 465-472

    • DOI

      10.1016/j.bbrc.2019.12.068

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effect of Lubricin Mimetics on the Inhibition of Osteoarthritis in a Rat Anterior Cruciate Ligament Transection Model2020

    • Author(s)
      Nemirov Daniel、Nakagawa Yusuke、Sun Zhexun、Lebaschi Amir、Wada Susumu、Carballo Camila、Deng Xiang-Hua、Putnam David、Bonassar Lawrence J.、Rodeo Scott A.
    • Journal Title

      The American Journal of Sports Medicine

      Volume: 48 Issue: 3 Pages: 624-634

    • DOI

      10.1177/0363546519898691

    • Related Report
      2020 Research-status Report
  • [Journal Article] Long-term Evaluation of Meniscal Tissue Formation in 3-dimensional-Printed Scaffolds With Sequential Release of Connective Tissue Growth Factor and TGF-β3 in an Ovine Model2019

    • Author(s)
      Yusuke Nakagawa, Lisa Fortier, Jeremy Mao, Chang Hun Lee, Margaret Goodale, Matthew Koff, Tyler Uppstrom, Brett Croen, Susumu Wada, Camila Carballo, Hollis Potter, Scott Rodeo
    • Journal Title

      The American Journal of Sports Medicine

      Volume: 47 Issue: 11 Pages: 2596-2607

    • DOI

      10.1177/0363546519865513

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Duration of Postoperative Immobilization Affects MMP Activity at the Healing Graft-Bone Interface: Evaluation in a Mouse ACL Reconstruction Model2019

    • Author(s)
      Yusuke Nakagawa, Amir Lebaschi, Susumu Wada, Samuel Green, Dean Wang, Zoe Album, Camilla Carballo, Xiang-Hua Deng, Scott Rodeo
    • Journal Title

      Journal of Orthopedic Research

      Volume: 37 Issue: 2 Pages: 325-334

    • DOI

      10.1002/jor.24177

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transplantation of Aggregates of Autologous Synovial Mesenchymal Stem Cells for Treatment of Cartilage Defects in the Femoral Condyle and the Femoral Groove in Microminipigs2019

    • Author(s)
      Shimpei Kondo, Yusuke Nakagawa, Mitsuru Mizuno, Kenta Katagiri, Kunikazu Tsuji, Shinji Kiuchi, Hideo Ono, Takeshi Muneta, Hideyuki Koga, Ichiro Sekiya
    • Journal Title

      The American Journal of Sports Medicine

      Volume: 47 Issue: 10 Pages: 2338-2347

    • DOI

      10.1177/0363546519859855

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Benefit of Subcutaneous Patient Controlled Analgesia After Total Knee Arthroplasty2019

    • Author(s)
      Yusuke Nakagawa, Toshifumi Watanabe, Yusuke Amano, Masafumi Horie, Tomomasa Nakamura, Koji Otabe, Mai Katakura, Ichiro Sekiya, Takeshi Muneta, Hideyuki Koga
    • Journal Title

      Asia-Pacific Journal of Sports Medicine, Arthroscopy, Rehabilitation and Technology

      Volume: 18 Pages: 18-22

    • DOI

      10.1016/j.asmart.2019.09.001

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒアルロン酸シート移植治療は膝蓋下脂肪体線維化を改善し、膝関節痛を軽減する ラットを用いた検討.2021

    • Author(s)
      曲 禎, 中川 裕介, 辻 邦和ら
    • Organizer
      日本整形外科基礎学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 前十字靱帯再建術後の膝蓋下脂肪体線維化は短期臨床成績を悪化させる.2021

    • Author(s)
      吉田 龍, 中川 裕介, 雨宮 正樹ら
    • Organizer
      日本整形外科学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Infra-patellar fat pad fibrosis is associated with elevation of inflammatory cytokines level in the synovial fluid and delays functional recovery in ACL-reconstructed patients2020

    • Author(s)
      Yusuke Nakagawa, Kunikazu Tsuji, Hideyuki Koga
    • Organizer
      ACL small study group meeting
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2023-01-30  

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